Prognostic Value of Pathological Response After Conversion Therapy and Salvage Surgery in Unresectable Hepatocellular Carcinoma

ABSTRACT Background and Aims To evaluate the prognostic significance of pathological response in patients with initially unresectable hepatocellular carcinoma (uHCC) who underwent salvage resection after successful conversion with lenvatinib, anti‐PD‐1 antibodies, and locoregional therapy (LPLRT). Methods This multicenter retrospective study included 102 uHCC patients who achieved curative resection after LPLRT across four tertiary centers in China. Residual viable tumour (pRVT) ratio was used to assess pathological response. Optimal pRVT cutoffs for overall survival (OS) and recurrence‐free survival (RFS) were identified using X‐tile (a statistical tool that identifies optimal prognostic cutoff values for continuous variables by systematically maximizing the log‐rank statistic). Survival was analysed by Kaplan–Meier and log‐rank tests, and prognostic factors by Cox regression analyses. Results Among 102 patients, 25 (24.5%) achieved pathological complete response (pCR). X‐tile identified pRVT thresholds of 10% and 35% as optimal for predicting OS and RFS, respectively. Patients with pRVT ≤ 10% had superior OS (1‐, 2‐, 3 year: 96.6%, 89.8%, 82.5%) compared with pRVT > 10% (95.5%, 73.0%, 49.4%; p = 0.002). pRVT ≤ 35% was associated with longer RFS (1‐, 2 year: 60.5%, 47.1% vs. 24.0%, 10.0%; p < 0.001). Similar trends persisted after excluding pCR cases. On multivariate analysis, NLR < 2.6, adjuvant therapy, and pRVT ≤ 10% independently predicted improved OS, while age < 60 years was adverse for RFS, and NLR < 2.6 and pRVT ≤ 35% were independently associated with prolonged RFS. No clinical variables predicted pRVT thresholds. Conclusions pRVT refines postoperative prognostic assessment in uHCC after multimodal conversion therapy. Thresholds of ≤ 10% for OS and ≤ 35% for RFS serve as practical cutoffs for postoperative risk stratification.